Conditional disruption of beta 1 integrin in Schwann cells impedes interactions with axons

J Cell Biol. 2002 Jan 7;156(1):199-209. doi: 10.1083/jcb.200109021. Epub 2002 Jan 3.

Abstract

In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell-specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. beta 1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and alpha 6 beta 4 integrin. These data suggest that beta 1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / pathology
  • Axons / ultrastructure
  • Bromodeoxyuridine / metabolism
  • Cell Adhesion
  • Cell Division / genetics
  • Cell Size
  • Cell Survival / genetics
  • DNA / biosynthesis
  • Gene Deletion*
  • Gene Expression Regulation*
  • In Situ Nick-End Labeling
  • Integrin beta1 / genetics*
  • Integrin beta1 / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Muscular Dystrophy, Animal / genetics
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / pathology
  • Muscular Dystrophy, Animal / physiopathology
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism
  • Myelin Sheath / ultrastructure
  • Organ Specificity
  • Receptors, Laminin / chemistry
  • Receptors, Laminin / genetics
  • Receptors, Laminin / metabolism
  • Schwann Cells / metabolism*
  • Schwann Cells / pathology*
  • Schwann Cells / ultrastructure

Substances

  • Integrin beta1
  • Receptors, Laminin
  • DNA
  • Bromodeoxyuridine